The detection of malignant melanoma with radiopharmaceuticals is limited by lack of specificity and inability to identify lesions less than 2.0 cm in size. We propose that the use of two short-lived radiopharmaceuticals (one melanin-seeking and the other tumor-seeking) and modifications in detection systems, will allow for improvement in clinical localization of melanoma. The use of short-lived radionuclides will substantially reduce the radiation dose. Quinoline analogs have melanin affinity. We have labeled one of them (4,3 dimethylaminopropylamino-7-iodoquinoline) with iodine-123 (half-life 13.3 hours, 159 kev gamma rays). We have visualized human skin melanoma and eye melanoma 3 and 6 hours after injection. Clinical trials are to be continued to define the usefulness of this agent. Combining this with another tumor-seeking agent, e.g., gallium-67 citrate (half-life 78 hours, four primary gamma rays, 93-388 kev should enhance diagnostic accuracy. The reliability of detecting melanin containing tumors, i.e., malignant melanoma, will be high. This information is particularly important in clinical practice, e.g., evaluating metastatic and ocular tumors. Similarly, the ophthalmologist faced with a mass inside the eye which cannot be biopsied would benefit from a non-contact method of evaluation. This would also avoid the eye surgery now done for the radio-active phosphorus uptake test. Modifications in radiation detection systems will be necessary to visualize small melanoma. A double pinhole collimator has been of limited success with the Anger scintillation camera for eye melanoma. A dual headed contact detection device and/or an ultrasound guided gamma probe is necessary for diagnosis of small intraocular masses. A positron ring system (PETT III) will be used with compounds labeled with positron emitting nuclides. Gallium-68 and iodine-124 (positron emitters) will be used as the citrate and quinoline compound respectively.